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  • 1
    ISSN: 1432-0428
    Keywords: Pancreatic islet cells ; cell suspensions ; islet cell surface antibodies ; cell surface immunofluorescence ; Protein A radioassay ; cell surface antigens ; autoimmunity ; diabetes mellitus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Rabbits were immunised with suspensions of viable, insulin-producing islet cells prepared from collagenase-isolated rat or ob/ob mouse pancreatic islets. Antibodies reactive with the surface of dispersed rat islet cells were present in both the rabbit anti-rat and the rabbit anti -ob/ob mouse islet sera as revealed by indirect immunofluorescence or by a radioligandassay using 125I-Protein A as a measure of cell bound IgG. In a competition assay the binding of 125I-Protein A was displaced in a concentration dependent manner by non-radioactive Protein A. Maximal displacement was found at concentrations of Protein A higher than 0.1 μg. added to 105 islet cells. Although not always detected by immunofluorescence there was a several-fold increase above normal rabbit serum of 125I-Protein A-binding to rat hepatocytes and spleen lymphocytes incubated with the islet cell antisera. Conversely, rabbit antisera against rat spleen lymphocytes or against a rat liver plasma membrane preparation reacted with rat islet cells. The rabbit anti-rat islet cell antiserum was absorbed to both spleen lymphocytes and hepatocytes until there was no binding of 125I-Protein A to either cell type. Islet specific antibodies were still present since this doubly absorbed antiserum induced cell surface immunofluorescence as well as 125I-Protein A-binding to rat islet cells. It is concluded that apart from common antigenic determinants immunisation with viable islet cells induces formation of antibodies directed against specific islet cell surface components.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Islet amyloid polypeptide precursors ; monkey (Macaca nemestrina) ; dog (Canis familiaris) ; amyloidogenic properties
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The 37-amino acid islet amyloid polypeptide represents the major protein component present in islet amyloid deposits. Although the presence of islet amyloid is a characteristic pathological feature of the islets of humans, monkeys and cats with Type 2 (non-insulin-dependent) diabetes mellitus, it is not found in the islets of diabetic rats, mice or dogs. To further explore the molecular basis for these species differences in amyloid deposition we have used a polymerase chain reaction based method to clone cDNAs encoding the monkey (Macaca nemestrina) and dog (Canis familiaris) islet amyloid polypeptide precursors. The predicted amino acid sequence of the monkey precursor is 96% identical to that of the human protein; differences include one replacement in the signal peptide and three in the islet amyloid polypeptide domain. The sequence of the dog precursor is most closely related to that of the cat protein (85% identity); the sequences of dog and cat islet amyloid polypeptide differ only at two positions and are identical in the region of amino acids 20–29, the region thought to be primarily responsible for amyloidogenesis. Thus, amino acid residues in addition to those at positions 20–29 may facilitate the aggregation of islet amyloid polypeptide. The presence of amyloid deposits in some dog pancreatic endocrine tumours suggests that the dog protein can be amyloidogenic, perhaps due to elevated expression of islet amyloid polypeptide by the tumours relative to normal islets.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 35 (1992), S. S41 
    ISSN: 1432-0428
    Keywords: Insulin gene ; expression ; precursor processing ; glucokinase ; glucose transport ; signal transduction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Considerable progress has been made in our understanding of islet-cell function and its relationship to regulation of whole body glucose metabolism. At the genetic level, the regulatory regions in islet-specific genes are being characterised. Transcription factors that interact with these regions have been cloned and these will be instructive in elucidating how islet-specific genes are regulated during development and regeneration. Identification of the enzymes responsible for proteolytic conversion of proinsulin to insulin represents a major advance in understanding prohormone processing. Cleavage of proinsulin is mediated by at least two prohormone convertases (PC3/PC1 and PC2). Their activity is regulated by an acidic gradient between the Golgi and secretory granules and by calcium ions. It is not yet clear how insulin or the PC's are specifically diverted into the regulated secretory pathway. Regulation at this step may be defective in some diabetic patients resulting in relatively elevated circulating proinsulin levels. Specific features of GLUT 2 and glucokinase (GK), proteins that regulate Beta-cell glucose transport and phosphorylation, indicate that these may be key components of the glucose sensor. GLUT 2 is necessary to reconstitute glucose-sensitive insulin secretion in pituitary tumour cells expressing a proinsulin cDNA. Furthermore, the expression of GLUT 2 in Beta cells, but not in hepatocytes, is decreased in diabetes mellitus. However, under normal circumstances GK is probably rate limiting for Beta-cell glucose utilisation. Thus, it is likely that both GLUT 2 and GK determine the set point for glucose-stimulated insulin secretion. Elucidation of distal effectors that regulate insulin secretion is also crucial to our understanding of Beta-cell function. Elevations in cytosolic Ca2+ are essential for stimulus secretion coupling. A novel second messenger, cyclic ADP ribose, has been implicated as a regulator of glucose-stimulated Ca2+ release from the Beta-cell endoplasmic reticulum. These and other recent advances provide optimism for the ultimate development of an artificial Beta cell capable of making insulin and releasing it in response to glucose.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0428
    Keywords: Islet amyloid polypeptide ; Type 2 (non-insulindependent) diabetes mellitus ; polymerase chain reaction ; direct sequencing ; maturity onset diabetes mellitus of the young (MODY) ; Pima Indian
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Islet amyloid polypeptide is the major protein component of the islet amyloid of patients with Type 2 (non-insulin-dependent) diabetes mellitus. Since the synthesis of a structurally abnormal or mutant protein may contribute to the formation of amyloid deposits, we have examined the possibility that a mutant form of islet amyloid polypeptide or its precursor contributes to the formation of islet amyloid in Type 2 diabetic patients. We have sequenced the islet amyloid polypeptide precursor coding regions of the gene of 25 patients with Type 2 diabetes. Genomic DNA fragments corresponding to exon 2 and 3 of the islet amyloid polypeptide gene were amplified from patients' peripheral blood leucocyte DNAs using the polymerase chain reaction and specific oligonucleotide primer sets, and then directly sequenced. The nucleotide sequences of the amplified regions of both alleles of the islet amyloid polypeptide gene of these 25 patients were identical to one another and to the sequence of an islet amyloid polypeptide allele isolated from a human fetal liver genomic library. These findings suggest that a primary structural abnormality of islet amyloid polypeptide or its precursor is unlikely to play a significant role in the formation of islet amyloid in Type 2 diabetic patients.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 0340-1855
    Keywords: Schlüsselwörter Radiosynoviorthese ; Aktivitätsabtransport ; Strahlenexposition ; arthroskopische Synovektomie ; Yttrium-90 ; Key words Radiation syno- ; vectomy ; activity leakage ; radiation exposure ; arthroscopic synovectomy ; yttrium-90
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary In rheumatic diseases, radiation synovectomy is a reliable method. Meanwhile, radiation synovectomy is an outpatient therapy. In addition, combination with arthroscopic synovectomy is an increasing therapeutic modality. In comparison to the hitherto inpatient modality, a greater lymphatic emigration of the radionuclide and, therefore, a higher radiation exposure is possible. In 35 patients we found radionuclide emigration in 17 cases by whole body scintigraphy, resulting in a 50%-percentile with 68.27%-confidence interval of 1.8 (0.45–4.78)% of the injected yttrium-90-activity. Comparison of 3 groups with the above mentioned therapy modalitites resulted in no statistical difference (p〉0.05). Because of the found radionuclide emigration, a radiation dose of 0.1 (0.05–0,18) mSv in women and 0.2 (0.1–0.38) mSv in men was calculated. For lymph nodes, liver, spleen and whole body radiation doses of 619 (154–1644) mSv, 62 (15–165) mSv, 62 (15–165) mSv and 37 (9–99) mSv were calculated. Gonadal radiation dose can be neglected and the morbidity rate for tumors bacause of the whole body radiation dose is low with a value of 0.4 per thousand. Therefore, radiation synovectomy can be used unlimited by patients age and independent of the therapeutic modality.
    Notes: Zusammenfassung Die bei entzündlich-rheumatischen Erkrankungen bewährte Radiosynoviorthese wird inzwischen zunehmend ambulant durchgeführt. Zudem wird sie immer häufiger zur Erfolgsverbesserung mit der arthroskopischen Synovektomie kombiniert. In beiden Fällen ist gegenüber der ursprünglich stationär durchgeführten Therapie eine Zunahme des lymphogenen Radionuklidabtransportes und damit der Strahlenexposition denkbar. Der Aktivitätsabtransport wurde bei 35 Patienten mittels Ganzkörperszintigraphie bestimmt, insgesamt ließ sich bei 17 Patienten ein Abtransport nachweisen. Die Patienten wurden in drei Gruppen unterteilt, die sich in den oben genannten Therapiemodalitäten unterschieden. Hierbei ergab sich kein statistisch wertbarer Unterschied des Aktivitätsabtransportes (p〉0,05) und der daraus resultierenden Strahlenexposition. Die 50%-Perzentile mit 68,27%-Vertrauensbereich des zu erwartenden lymphogenen Aktivitätsabtransportes ergab sich zu 1,8 (0,45–4,78)% der injizierten Yttrium-90-Aktivität. Daraus errechnete sich unter Berücksichtigung der vom therapierten Kniegelenk ausgehenden Bremsstrahlung eine Gonadenexposition von 0,1 (0,05–0,18) mSv für Frauen und von 0,2 (0,1–0,38) mSv bei Männern. Für Lymphknoten, Leber, Milz und Ganzkörper ergab sich eine Strahlenexposition von 619 (154–1644) mSv, 62 (15–165) mSv, 62 (15–165) mSv und 37 (9–99) mSv. Das aus der Gonadenexposition resultierende genetische Risiko ist vernachlässigbar klein. Das aus der Ganzkörperexposition resultierende Tumormorbiditätsrisiko ist mit 0,4 Promille ebenfalls gering. Somit ergibt sich auch unter Berücksichtigung bisher fehlender Berichte über Tumorerkrankungen in Zusammenhang mit der Radiosynoviorthese keine generelle Notwendigkeit, die Anwendung altersabhängig bzw. abhängig von der Therapiemodalität zu beschränken.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Sensors and Actuators B: Chemical 5 (1991), S. 161-164 
    ISSN: 0925-4005
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology , Electrical Engineering, Measurement and Control Technology
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Fusion Engineering and Design 4 (1987), S. 211-222 
    ISSN: 0920-3796
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Energy, Environment Protection, Nuclear Power Engineering , Physics
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 0920-3796
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Energy, Environment Protection, Nuclear Power Engineering , Physics
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Fusion Engineering and Design 23 (1993), S. 157-172 
    ISSN: 0920-3796
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Energy, Environment Protection, Nuclear Power Engineering , Physics
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 0920-3796
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Energy, Environment Protection, Nuclear Power Engineering , Physics
    Type of Medium: Electronic Resource
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